Andrea Rinaldi and Priya Shetty review the facts, figures and challenges of mixing modern and traditional medicine.

For millennia, people have healed with herbal or animal-derived remedies, using knowledge handed down through generations.

In Africa, Asia, Latin America and the Middle East, 70-95 per cent of the population still use traditional medicine (TM) for primary healthcare. And some 100 million people are believed to use traditional, complementary or herbal medicine in the European Union (EU) alone — as high as 90 per cent of the population in some countries. [1]

Desperately seeking drugs

Meanwhile, modern medicine is desperately short of new treatments. Drugs take years to get through the research and development pipeline, at enormous cost. And rising drug resistance, partly caused by misuse of medicines, has rendered several antibiotics and other life-saving drugs ineffective. So scientists and pharmaceutical companies are increasingly searching TM for new drug sources.

A few triumphs have stoked this interest. The best known is artemisinin, used to treat malaria (see Box 1).

Box 1: Artemisinin: traditional medicine’s blockbluster drug

Artemisinin, which is extracted from Artemisia annua (Chinese sweet wormwood), is the basis for the most effective malaria drugs in the world.

Long-used in China, the medicine was first noticed by Western researchers in the 1980s. But its worldwide use wasn’t endorsed by the WHO until 2004, largely because of scepticism: research groups spent years validating the claims of Chinese traditional healers.
Artemisinin is also proving useful against other diseases, including cancers and schistosomiasis.

But it is showing signs of fallibility. There are reports of growing resistance to artemisinin in South-East Asia, and fears that if resistant parasites spread to Africa they could trigger a public health catastrophe.

Across the globe, researchers, policymakers, pharmaceutical companies and traditional healers are joining forces to bring TM into the twenty first century.

In some ways, it is already here. Nearly a quarter of all modern medicines come from natural products, many of which were first used in traditional remedies (see Table 1). And of 121 prescription drugs used worldwide against cancer, 90 are derived from plants. [5]

Traditional Middle Eastern remedy for asthma. Also traditionally used in Egypt to treat kidney stones

Etoposide

Anticancer

Synthesised from podophyllotoxin, produced by the American mandrake plant

Various remedies in Chinese, Japanese and Eastern folk medicine

Hirudin

Anticoagulant

Salivary glands in leeches, now produced by genetic engineering

Traditional remedies across the globe, from Shui Zhi medicine in China to eighteenth and nineteenth century medicine in Europe

Lovastatin

Lowers cholesterol

Foods such as oyster mushrooms and red yeast rice, also used to synthesise other compounds such as pravastatin

Mushrooms are used to treat a wide range of illnesses in traditional medicine in China, Japan, Eastern Europe and Russia

Opiates

Painkilling

Unripe poppy seeds

Traditional Arab, Chinese, European, Indian and North African medicines as pain relief and to treat a range of illnesses including diarrhoea, coughs and asthma

Quinine

Antimalarial

Bark of the cinchona tree

Traditional remedies to treat fevers and shivers in South America

Vinca alkaloids (vincristine, vinblastine)

Anticancer

Synthesised from indole alkaloids produced by the rosy periwinkle

Folk remedies across the world use periwinkle plants, including as an antidiabetic in Jamaica and Madagascar, to treat wasp stings in India, as eyewash in Cuba, as love potion in medieval Europe

Modernising tradition

But efforts to incorporate TM’s knowledge into modern healthcare and ensure it meets safety and efficacy standards are far from complete. And conservationists worry that a growing TM market threatens biodiversity by overharvesting medicinal plants or using body parts from endangered animals (see Box 2).

Box 2: The impact of traditional medicine on nature conservation

The growing demand for TM ingredients is endangering some animals. Rhino poaching is resurging after anecdotal claims that rhino horns can treat cancer [7]. Horns are illegally traded, especially in Vietnam and China, fetching thousands of dollars (up to US$50,000 a kilogram in 2009). The numbers of black and white rhinos in Africa are dwindling fast.

Tigers fare badly too — just 3,000 may be left in East and South Asia. Their bones and other body parts have long been used in traditional Asian medicine. Despite China’s 1993 ban, the trade has continued and is now fuelled by the country’s expanding wealthy classes.

But TM’s impact on wildlife goes beyond endangered species and is vastly under-documented. A recent study in Kenya showed that plants for local medicinal use are almost exclusively harvested from the wild, and much more material is used than previously thought. Rural poverty and weak health systems are driving forces: interviews found about 60 per cent of market traders selling medicines in Nairobi, Mombasa and Kisumu said using natural resources for TM was their only source of household income. [8]

There are ways to prevent overexploitation. This film shows how Shamli village, in the Indian state of Maharashtra, has successfully revived local use of traditional herbal medicines to preserve the forest and its plants. It did this through partnerships, by producing an inventory of plants and by promoting ownership by local people, particularly women.

Integration also faces other challenges stemming from key differences in how traditional and modern medicine is practised, evaluated and managed (see Table 2).

Table 2: Key differences between traditional and modern medicine

Traditional medicine

Modern medicine

Knowledge protection

Open access but social or legal restrictions may govern who can use certain knowledge, under what conditions and with what benefit for knowledge holders

Usually loose. In some cases with restrictions on use or dissemination. Rules and standardisation are being introduced but vary between countries

Extremely tight

Testing

No formal testing: understanding of effectiveness is handed down through generations

Rigorous trials that happen in different phases (first testing for safety, then efficacy) mean bringing a drug to market costs billions of dollars

Dosage

Unfixed: the amount of medicine given might be roughly similar, but the amount of active ingredient (which is what dosage really is) can vary hugely

Standardised medicines given in fixed doses that vary with age or weight, or disease severity

Consultation

Lengthy, and the patient is asked a wider range of questions than just about their symptoms

Consultations in both primary and secondary care tend to be brief and focused, especially as national health systems come under financial strain

Training

Lengthy training over many years but knowledge is often passed one-to-one through families, and practitioners are often born into a family of healers

Lengthy and often vocational: health professionals go through formal training in schools and universities

Inherently variable

It can be extremely difficult to apply modern tests — developed for standardised drugs — to TM’s inherently diverse range of products.

Many traditional medicines are made by crushing leaves or bark, and the resulting mixture can contain hundreds of potentially active molecules. Identifying these is hard enough, and testing each one for safety and effectiveness is practically impossible.

Unlike many modern pharmaceuticals, the quality of material for traditional medicines varies enormously between, and even within, source countries and plants. This is both because of genetic differences and other factors such as environmental conditions, harvesting, transport and storage.

Dosage is similarly varied. Modern medicine demands dosages that are standardised based on factors such as bodyweight or disease severity. Traditional healers are more likely to give patients a unique dosage or combination of medicines that is decided during the consultation.

So when modern evaluations of traditional drugs give poor results, it may be due to many factors: from mistakenly using the wrong plant to contamination or dosing problems.

Protection and biopiracy

Perhaps the most striking difference between traditional and modern medicines is the legal protection given to knowledge. Traditional practitioners have historically shared their knowledge and experience freely — defining ‘open-access’ before the term even existed. Modern medicine, on the other hand, has stringent intellectual property laws and a highly evolved protective patenting system.

Scientists searching indigenous sources for new drugs — ‘bioprospecting’ — have to navigate these differences.

Researchers have sometimes sought patents for compounds that had already been used for centuries. An example is the 1995 patent on an antifungal neem derivative commonly used in Indian traditional remedies. The European Patent Office (EPO) granted a patent to the US Department of Agriculture and the multinational WR Grace and Company. It took the Indian government five years and millions of dollars to convince the EPO to revoke the patent on the basis of prior use.

Plundering unprotected indigenous resources has been termed ‘biopiracy’ and highlights the challenges facing efforts to integrate traditional and modern approaches to medicine.

Legal frameworks and sharing benefits

There is an urgent need for both global and local legal frameworks to regulate bioprospecting activities and avoid biopiracy. However, protecting intellectual property (IP) rights of indigenous peoples and local communities to traditional medical knowledge is a thorny issue.

Schemes that provide IP protection in the classic sense — against unauthorised use by third parties — are seldom easy to apply to traditional knowledge systems because their property/non-property distinctions rarely fit indigenous cultures. Also, patent protection is typically time-limited, while traditional medical knowledge should be protected retroactively or indefinitely or both.

Further, IP protection must not restrict people’s access to traditional medical practices that are a form of cultural expression. And it must allow research and innovation that enhances traditional medicine’s status as a healthcare option.

The problem is so complex that the World Intellectual Property Organization (WIPO) has established an ad hoc committee to develop an international legal instrument to protect traditional medical knowledge, and address the IP aspects of benefit-sharing and access to genetic resources.

The Nagoya Protocol is an existing international legal tool that offers some protection for traditional knowledge of medicines. The protocol came in to force on 12 October 2014 as a supplement to the Convention for Biological Diversity (CBD), and was ratified by 59 countries and the EU. Its main objective is to equitably share the benefits gained from using genetic resources and it clearly addresses the associated rights of indigenous communities. It forces countries to ensure that anyone under their jurisdiction who benefits from traditional knowledge has obtained prior informed consent and negotiated a fair and equitable deal to share those benefits.

And South Africa’s implementation of the protocol has enabled the indigenous San people to negotiate agreements with companies that profit from traditional medicines (see Box 3).

Box 3: The San Bushmen of the Kalahari and benefit sharing

For the San people of southern Africa, the path to benefit sharing began with controversy around the Hoodia gordonii plant, used for centuries by the San to stave off hunger and thirst. South Africa’s Council for Scientific and Industrial Research (CSIR) patented the plant’s hunger-suppressing component (known as P57) in 1996, then licensed it to the UK firm Phytopharm, which then licensed it to Pfizer to be developed as a weight-loss drug. No benefits were earmarked for the San, who were controversially described by a Pfizer spokesperson as “extinct”. After challenges from the San people, a 2002 agreement, one of the first benefit-sharing agreements of this kind, acknowledged and rewarded them with a percentage of the profits from commercial exploitation. The patent was later sold to Unilever, but the company abandoned plans for its development. [9]

But there are recent successes. The San people have reached a benefit-sharing agreement with HG&H pharmaceuticals. The company developed the Sceletium tortuosum plant as an antidepressant and antianxiety extract, marketed as Zembrin. Researchers identified the active component, and Zembrin products entered the market in 2012.

And in 2014, an agreement with the firm Cape Kingdom ensured that the San and Khoi communities receive a share of the revenue from sale of health products based on the Agathosma betulina plant, locally known as buchu.

According to Doris Schroeder, ethics professor at the UK’s University of Central Lancashire, who has undertaken extensive research into benefit sharing, such agreements are a welcome step towards promoting justice for disadvantaged people in the developing world. [9]

Rewards from modern uses of South Africa’s buchu plantIf you are unable to listen to this audio, please update your browser or click here to download the file [15.8MB].

But about half the countries that responded to a global survey in 2012 reported regulating traditional and complementary medicine practitioners, and there are several obstacles to effective regulation (see Figure 2). [2]

And traditional medicine often means different things to different people. A single medicinal plant may be classified as a food, a dietary supplement or a herbal medicine.

Education and research have also advanced. Some 39 countries now provide high-level education and training programmes on traditional medicine (see Figure 3).

Room for improvement

But much still needs to be done before a global standard for TM is agreed. Loose regulation means there are as many fake remedies and false practitioners as genuine treatments and practitioners. It is often difficult to distinguish between traditional treatments backed by research and those with unproven claims or even ‘extras’ that may lead to harm.

Contaminated and adulterated products are common. Many herbal products, especially those purchased online, contain toxic heavy metals such as lead, mercury and arsenic. [13] Conventional drugs such as Viagra and estrogens are sometimes added to herbs, to make them ‘more effective’. [13]

All this exacerbates concerns over unknown but potentially harmful drug-herb interactions —and over substituting tested conventional with untested herbal medicine.

A key first step, according to the WHO, is to acknowledge the role TM already plays in people’s healthcare, identifying which forms are most popular, and whether people rely on TM on their own or seek advice from health professionals.

Testing times

Like regulation, methods for evaluating and testing medicines also vary widely.

Modern drugs go through rigorous laboratory tests and clinical trials designed to prove effectiveness, test for safety and standardise manufacturing practices. In contrast, traditional medicines undergo few scientific tests, production standards tend to be less rigorous or controlled, and practitioners are often not certified or licensed.

Some argue that drugs which have been tried and tested in thousands of people for decades or centuries don’t need the same tests as a brand new chemical. And some argue that traditional knowledge is itself a science.

But many agree that traditional medicines need reassessment before being integrated into a conventional framework of pharmaceuticals. Sometimes, this requires standard methods to adapt to cope with ethical issues that do not arise with conventional drug development. US researchers Jon Tilburt and Ted Kaptchuk have, for example, suggested that clinical trials of traditional medicines must follow different ethical rules (see Box 4). [14]

Box 4: Rules of research ethics for clinical trials of traditional medicines*

Justifiable social need for the research

The rationale for trialling a traditional medicine cannot simply be that it already exists as a treatment. There must be both a social need and some preliminary evidence that the medicine will not counteract other conventional medicines used to treat the same disease. Stakeholders will define social need in varying ways — for example a government may want to prevent any other party from commercialising the treatment and health campaigners may want the clinical trial to try to produce better drugs.

Appropriate definitions of inclusion and exclusion criteria, and outcome measures

Concepts of health and sickness differ between modern and traditional medicine. For example, Western researchers would use the New York Heart Association classification for heart failure, but traditional Chinese medicine (TCM) practitioners would see heart failure as a heart yang chi deficiency or a kidney yang deficiency, categorising patients based on pulse or tongue examination. Researchers testing a herbal remedy for heart failure would need to take both biomedical and TCM criteria into account for the results to be valid from both perspectives.

Innovative protocol design

Drugs brought to market by putting traditional medicines through clinical trials must be rigorously tested, but standard methodologies may not be appropriate for a medicine that contains a mixture of active ingredients or in treatments that vary between practitioners. Standard protocols could adapt to accommodate many of these issues.

Establishing standards for safety and evidence

The familiarity of traditional medicines, and their widespread use, could lead some researchers to wrongly assume they are safe. Care is needed early on to determine safety requirements.

Table 3: How to create modern drugs from traditional compounds [15,16]

Technique

Process

Reverse pharmacology

Researchers start with the end product, a clinically useful compound for example, and work backwards to find out what it contains and how it functions. This can offer clues about how a medicine works and where it acts in the body

The systematic study of how specific ethnic groups use medicinal plants

Systems biology

A holistic approach aiming to understand how chemicals and metabolic processes interact in the body. It could be used to measure the whole body's response to the mixtures of active compounds often found in TM

Genome mining

This searches a genome (often a microbe’s) for DNA sequences that encode enzymes involved in synthesising biologically active natural products. The active ingredients of some medicinal plants are actually made by microorganisms living within the plant

Metabolomics

This offers a rapidly advancing approach to drug discovery that can systematically study how a complex mixture, such as a plant extract, is metabolised in the body, and so identify bioactive secondary metabolites

Gaining ground

Top research bodies worldwide are serious about integrating traditional medicine into modern healthcare. And many countries are working actively to harness and regulate TM.

The US National Institutes of Health, for example, houses an organisation called the National Center for Complementary and Alternative Medicine (NCCAM) that funds research into how acupuncture, herbal supplements, meditation or osteopathy can help treat conditions such as cancer, cardiovascular disease and neurological disorders.

Developing countries with ancient histories of traditional medicine are also hunting for ways to modernise their own medical heritage. In China, modern and traditional medicine are practised alongside each other throughout the healthcare system. The government gives equal weight to developing both and China has a large and active research community on ‘integrative medicine’.

In February 2013, India and the WHO South-East Asia Regional Office organised an international conference that agreed the Delhi Declaration on Traditional Medicine, which aims to collaborate and strengthen TM’s role in health.

Certainly, traditional medicine has much to offer global health. If both developed and developing countries joined research capacities in equitable collaborations, new scientific techniques could spark a revival in global health research and development.

The modern, mainstream system of medical practice in Western countries. It targets disease with remedies that treat or suppress symptoms or the condition itself. It tends to produce effects different from those produced by the disease under treatment.

Complementary/alternative medicine

The terms complementary and alternative medicine are sometimes used interchangeably with the term traditional medicine. They refer to the healthcare practices that are not part of a country’s own tradition and are not integrated into the dominant healthcare system.

Herbal medicines

These include herbs, herbal materials, preparations and products that contain plant materials or combinations of plants as active ingredients. Herbalism is the practice of making or prescribing plant-based herbal remedies for medical conditions and is considered a form of alternative medicine.

Integrative medicine

The term refers to the blending of conventional and natural/complementary medicines and/or therapies along with lifestyle interventions in a holistic approach, taking into account the physical, psychological, social and spiritual wellbeing of the person.

Traditional medicine

The overall body of knowledge, skills and practices based on the theories, beliefs and experiences indigenous to different cultures, whether they can be explained or not. These might be used to maintain health as well as prevent, diagnose, improve or treat physical and mental illness.